IGF-1 AND IGFBP-3 REMAIN HIGH AFTER TREATMENT-INDUCED PUBERTAL ARREST IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY (CPP)

Insulin like growth factor-1 (IGF-1) increases during normal adolescence and in CPP secondary to the rise in sex steroids and GH. Treatment of CPP using GnRH analog suppresses GH as well as gonadotropins. We examined IGF-1 and its major binding protein-IGFBP-3 in sera of ten girls diagnosed with CPP, before and during the first 3 months of GnRH analog therapy. Serum IGF-1 was increased in patients with CPP as compared with controls (48.8 + 6.5 vs 23.1 + 4.9 nmol/L, p < 0.01). GnRH analog therapy caused serum E2 levels to return to prepubertal levels in all 10 patients, whereas serum IGF-1 levels decreased minimally after one (43.2 ± 5.6 nmol/L), two (42.3 ± 6.4 nmol/L), and three (44.1 ± 7.2 nmol/L) months of therapy. Serum IGFBP-3 concentrations measured using IRMA were also higher in CPP compared with controls (4.7 ± 0.37 vs 3.7 ± 0.42 mg/L p < 0.01). These differences were also evident when all IGF binding proteins were measured by Western ligand blotting. GnRHa therapy caused a small and insignificant decrease in serum IGFBP-3 levels after one (4.57 ± 0.33 mg/L), two (4.48 ± 0.4 mg/L) and three (4.42 ± 0.3 mg/L) months of therapy. This lack of suppression of both IGF-1 and IGFBP-3 despite therapy which halts pubertal progression and reverses GH secretion underscores the complex regulation of IGF-1 and its binding proteins during puberty.